ABSTRACT NUMBER: ESOC2026A1935 CADASIL.PT: DISEASE SEVERITY STAGING IN A PORTUGUESE COHORT OF PATIENTS

Abstract Background and aims CADASIL is the most common monogenic cerebral small vessel disease and an important cause of ischemic stroke and vascular cognitive impairment in young and middle-aged adults. We aimed to characeterize and evaluate clinical severity of CADASIL in Portugal. Methods We conducted a cross-sectional, multicenter, study including patients with CADASIL and asymptomatic carriers of a NOTCH3 mutation. Demographic, genetic, and clinical data were obtained and brain MRIs were reviewed. Condition severity was assessed by CADASIL Clinical Severity Grading Scale and NOTCH3-SVD Staging System. Statistical analysis was performed using SPSS®. Results We included 138 individuals, 16% asymptomatic carriers of NOTCH3 mutation, 62.3% females, median age of 62 years (IQR 15). Family history of CADASIL was present in 58% of cases. Pathogenic variants c.1672C>T p.(Arg558Cys) and c.1258G>T p.(Gly420Cys) were the most frequently identified. Ischemic stroke and transient ischemic attacks were the predominant clinical presentations. Cognitive impairment and migraine-like headache was observed in 42% and 30% of cases, respectively. Two or more additional cerebrovascular risk factors were present in 60% of cases. Antiplatelet agents, statins and antidementia medication were taken by 66%, 57% and 20%, respectively. High disease severity (stage ≥3) was identified in 20% of cases. Stages 1 and 2 were obtained with the NOTCH3-SVD Staging System in 40% and 30% of cases of asymptomatic carriers, respectively. Conclusions This cohort highlights the high burden of CADASIL in Portugal and suggests a clinico-radiological mismatch in early stages. Early diagnosis may facilitate timely vascular risk factor management and improve neurological outcomes. Conflict of interest Carla Morgado: nothing to disclose, Aurora Costa: nothing to disclose, Daniela Ferro: nothing to disclose, Jorge Machado: nothing to disclose, Mariana Henriques: nothing to disclose, Mariana Perdicoulis: nothing to disclose, Sofia Pinto: nothing to disclose, Bárbara Rodrigues: nothing to disclose , Inês Carvalho: nothing to disclose , José Fins: nothing to disclose , Luís Costa: nothing to disclose , Beatriz Marques: nothing to disclose, Mariana Gomes: nothing to disclose, Miguel Peliteiro: nothing to disclose, André Rego: nothing to disclose, Maria João Lima: nothing to disclose, Luís Maia: nothing to disclose, Elsa Azevedo: nothing to disclose, Miguel Viana-Baptista: nothing to disclose, Ana Rita Silva: nothing to disclose